1. Field of the Invention
The present invention relates to an iontophoresis device for epidermal application. More specifically, it relates to an iontophoresis device having a light weight and capable of direct and very easy application to the human skin, without causing undesirable irritation in the skin.
2. Description of the Prior Art
Recently, iontophoresis has gained increased attention as an effective method for topical application of ionic agents or drugs by promoting absorption through the skin. Iontophoresis techniques are disclosed in, for example, Glass J. M. et al., Int. J. Dermatol. 19,519 (1980); Russo J., Am. J. Hosp. Pharm. 37,843 (1980); Gangarosa L. P. et al., J. Pharmacol. Exp. Ther. 212,377 (1980); Kwon B. S. et al., J. Infect. Dis 140,1014 (1979); Hill J. M. et al., Ann. NY. Acad. Sci. 284,604 (1977), and Tannebaum M. Phys. Ther. 60,792 (1980).
The iontophoresis disclosed in these prior arts is usually carried out by connecting the output terminal of a continuous direct current generator or pulsed direct current generator to a first or working electrode composed of a metal plate or other conductive substances covered with a moistened pad of porous material impregnated with an aqueous solution of ionic drug and a second or counter electrode structured similar to the first electrode but not soaked with the drug. From the above, it is clear that actual application of iontophoresis through these prior art techniques is very difficult, and while iontophoresis is a very effective method for drug application, this difficulty in application has prevented its use from becoming widespread.
Furthermore, the iontophoresis is generally applied to the human skin by using a continuous or pulsed direct current having the same polarity as that of the drug to be applied. However, the human skin S has ohmic resistance Rdc and a polarization impedance Z comprising (i) polarization resistance Rpol and (ii) polarization capacity Cpol, as shown in FIG. 1, which illustrates a skin equivalent circuit diagram. For example, where conventional iontophoresis utilizes a continuous direct current in which the ohmic resistance Rdc is solely used as a current path, a high voltage must be applied to the human skin to introduce the necessary amount of the drugs for treatment since the ohmic resistance Rdc is very high. The application of a high voltage to the human skin tends to strongly irritate the human skin, which causes burns and rubefaction in the skin. If a low voltage is applied to prevent these problems in the skin, the application of the necessary amount of the drugs becomes very difficult.
Furthermore, the ohmic resistance Rdc of the human skin S has a value of approximately 10 k.OMEGA..multidot.cm to 1 M.OMEGA..multidot.cm, which does not depend upon the frequency of the electric source, whereas it is known in the art that the polarization impedance Z substantially converges to zero when the frequency of the electric voltage used is, for example, 10 kHz or more (Yamamoto et. al., Med. & Biol. Eng. & Comput., (1978), 16, 592-594; Yamamoto et. al., Japanese Journal of Medical Electronics and Biological Engineering (1973), 11, No. 5, 337-342).
Accordingly, when a voltage having a high frequency is applied to the human body, the iontophoresis can be carried out under a low voltage since the polarization impedance Z is decreased. However, the polarization impedance Z of the skin S forms a parallel circuit, together with the polarization resistance Rpol and the polarization capacity Cpol, as shown in FIG. 1. For this reason, when a direct current pulse as shown in FIG. 2a is applied to the human skin, the electric current to be utilized in the introduction of the drugs is not substantially changed, compared with the case where a continuous direct current is applied as shown in FIG. 2b, because the polarization capacity is repeatedly charged and discharged and the charged residual charge (or polarization) is gradually but very slowly discharged (or depolarized) via the polarization resistance Rpol during the no pulse output periods. Consequently, a decrease in the skin impedance cannot occur even when a direct current pulse having a high frequency is applied.
Furthermore, as shown in FIG. 2C, even when the output time period of the direct current pulse is shortened to cause residual charge (or polarization) due to the polarization capacity Cpol, it is expected that the skin impedance Z will be lowered by widening the intervals of the no pulse output period (i.e., decreasing the so-called duty ratio) to sufficiently decrease the electric current value. However, an improvement in the drug introduction efficiency is not expected because the residual charge (or polarization) is the charge remained on the skin, which is not concerned with the drug introduction.